Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In ß-Cells With Improved Aqueous Solubility

Stephen Shane Scully; Alicia J Tang; Morten Lundh; Carrie M Mosher; Kedar M Perkins; Bridget K Wagner

doi:10.1021/jm400397x

Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In ß-Cells With Improved Aqueous Solubility

Stephen Shane Scully, Alicia J Tang, Morten Lundh, Carrie M Mosher, Kedar M Perkins, Bridget K Wagner

Endocrinology and Metabolism

20 Citations (Scopus)

Abstract

We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced β-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogues with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogues with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that 1 and analogues inhibit STAT1 signal transduction induced by IFN-γ.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	10
Pages (from-to)	4125-4129
Number of pages	6
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm400397x
Publication status	Published - 23 May 2013

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AU - Lundh, Morten

AU - Mosher, Carrie M

AU - Perkins, Kedar M

AU - Wagner, Bridget K

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Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In ß-Cells With Improved Aqueous Solubility

Abstract

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